Vitamin D deficiency in adulthood: Presentation of 2familial cases simulating pseudohypoparathyroidism

Background and objective: The clinical and biochemical overlap of various pathologies of phosphocalcic metabolism can lead to misdiagnosis and consequent clinical management. One example is pseudohypoparathyroidism, which can be confused with vitamin D-dependent rickets (VDDR1) if appropriate biochemical determinations are not performed.

Patients and methods: Two pairs of siblings, from independent families, were clinically diagnosed in adolescence with pseudohypoparathyroidism due to hypocalcaemia, elevated parathyroid hormone levels and normal or elevated phosphorus values. After ruling out alterations in GNAS, a massive sequencing study of genes associated with other differential diagnoses was carried out.

Results: Two genetic variants in the CYP27B1 gene potentially associated with the phenotype were identified. Pathogenic variants in this gene are associated with VDDR1A. Clinical-biochemical re-evaluation of the patients confirmed this diagnosis and treatment was adapted.

Conclusions: Although VDDR1A is an infrequently diagnosed pathology in adulthood, in cases of hypocalcaemia with elevated PTH values, determination of the 1,25(OH)₂D₃ and 25(OH)D₃ forms of vitamin D is relevant to reach a correct diagnosis.